Monoamine oxidase in rat arteries: evidence for different forms and selective localization

Abstract

Summary1. Two forms of monoamine oxidase activity were differentiated in rat mesenteric and femoral artery by means of substrate and inhibitor specificities: one form deaminated tyramine, 5-hydroxytryptamine and noradrenaline and was highly sensitive to pargyline and clorgyline but resistant towards carbonyl reagents. This form resembled type A monoamine oxidase previously described. The other deaminated tyramine but not 5-hydroxytryptamine or noradrenaline and was inhibited by carbonyl reagents but not by clorgyline or pargyline. 2. About one third of the total monoamine oxidase in homogenates of rat mesenteric artery was recovered in a 105 g supernatant. Both forms were partially soluble, but relatively less of the type A activity was recovered in the soluble fraction. 3. Chemical sympathectomy with 6-hydroxydopamine resulted in a loss of 59% of monoamine oxidase activity in the mesenteric artery. There was a selective loss of type A activity, as revealed by the 70% decrease in 5-hydroxytryptamine deaminating ability and by the marked decrease in clorgyline sensitivity. The second monoamine oxidase species was resistant to 6-hydroxydopamine. The soluble activity was not affected by chemical sympathectomy. Most of the transmitter-specific monoamine oxidase of the arterial wall was localized within the adrenergic nerve endings. Our observations are consistent with the hypothesis that extraneuronal monoamine oxidase plays only a minor role in metabolizing noradrenaline in sympathetically innervated tissues. 4. Plasma amine oxidase might originate from the arterial wall since it has similar characteristics to that found in the mesenteric artery.

Tyramine Antagonistic Properties of Agn 1135, an Irreversible Inhibitor of Monoamine Oxidase Type B

“…At a concentration of 1 x 10-6 M, selectivity for PEA oxidation was optimal, whereas concentrations of 1 X 10-M and above of (-)-deprenyl caused almost complete inhibition of both PEA and 5-HT deamination (Figure 8). (Kopin, 1964), and evidence exists that this MAO may be mainly of type A (Neff & Goridis, 1972;Coquil, Goridis, Mack & Neff, 1973 in heart and mesenteric artery and potentiated the cardiovascular effects of amphetamine (Simpson, 1978b) (Fuller, 1978). Concentrations of AGN 1135 and (-)-deprenyl above 10-;M caused almost complete inhibition of MAO types A and B and also resulted in potentiation of contractile effects of tyramine in the vas deferens, following wash-out of the inhibitors from the bath.…”

Metabolism of amines in the isolated perfused mesenteric arterial bed of the rat

“…Rat blood vessels possess an amine oxidase activity capable of metabolising tyramine (Tyr), which has different properties from monoamine oxidase (MAO; EC 1.4.3.4) enzymes (Coquil et al, 1973). This enzyme activity is insensitive to inhibition by clorgyline but is inactivated by carbonyl reagents such as semicarbazide and, as a result, is called semicarbazide-sensitive amine oxidase (SSAO).…”

“…When used in this way, it has been shown to inhibit SSAO selectively without affecting MAO-A in rat blood vessels (Elliott et al, 1989a). Although this inhibitor also inhibits MAO-B (Zreika et al, 1984), evidence from homogenates of rat mesenteric blood vessels suggests there is little or no MAO-B present in this tissue (Coquil et al, 1973;Fuentes & Neff, 1977 In these experiments, the metabolism was expressed as a percentage of a control, which had been preincubated in the absence of clorgyline.…”

“…In order to examine such a possibility, the isolated perfused mesenteric arterial bed of the rat was chosen to determine whether, or not, SSAO is capable of metabolizing substrates present in the fluid perfusing these vessels. Tyr was chosen as a suitable amine for study because it is metabolized by both SSAO and MAO-A in homogenates of these vessels (Coquil et al, 1973). The relative contribution of these two enzymes to the production of metabolites appearing in the perfusate could then be assessed.…”

“…Rat blood vessels possess an amine oxidase activity capable of metabolising tyramine (Tyr), which has different properties from monoamine oxidase (MAO; EC 1.4.3.4) enzymes (Coquil et al, 1973 Callingham & Barrand 1987, for review). SSAO has been shown to reside in the plasma membrane of vascular smooth muscle cells (Wibo et al, 1980;Lyles & Singh, 1985).…”